BACKGROUND: Mucus plugging has been identified as an important feature of severe asthma contributing to airway obstruction and disease severity. Recently, improvement in mucus plugging has been found on treatment with several biologic therapies. OBJECTIVES: To analyze associations of baseline characteristic with the mucus plugging score (MPS) and to determine whether the MPS at baseline predicts the clinical and functional response to biologic treatment in patients with severe asthma. METHODS: We retrospectively analyzed biologic-naive patients with a suitable computed tomography scan available at baseline. We calculated the MPS and analyzed correlations with baseline parameters and improvements in biomarkers, pulmonary function, and clinical parameters after 4 months of biologic therapy. RESULTS: We included 113 patients in the baseline cohort, 101 patients of whom had sufficient data after 4 months of biologic therapy for the follow-up analysis. Computed tomography showed mucus plugging in 77% of patients (median MPS, 4). Multivariate regression analysis showed a correlation of MPS with lower FEV CONCLUSION: Our study suggests that a higher MPS correlates with worse pulmonary function at baseline but also predicts a larger clinical and pulmonary function response to biologic therapies in severe asthma.